Across a variety of sensory systems, the cerebral cortex is known to be capable of responding to sensory loss with immediate reorganization of single neuron responses and functional maps. The rapid time course of these initial changes suggest prompt alterations in the properties of existing synaptic connections, though the circuit location and molecular mechanism of this form of rapid plasticity remains unknown. The current proposal hypothesizes that the first changes in circuit plasticity associated with sensory loss and diminished feedforward drive occur in layer 2/3, and involve a homeostatic upregulation of existing horizontal connections, many of which are long-range projections that confer response properties from other cortical columns onto affected neurons. This hypothesis makes specific predictions for what changes in single neuron response properties and feature maps should ensue upon focal modulation of feedforward drive, and presents a method for systematically and reversibly modulating this drive experimentally. The hypothesis also suggests that specific changes in the function of existing synapses should underlie observed changes in feature maps, and provides an in vitro framework by which to characterize these synaptic changes. Understanding the locus, mechanisms and dynamics of these first plastic changes associated with dramatic shifts in input drive will provide crucial insight into the possibility of utilizing intracortical network features to facilitate sensorv processing in the face of sensorv loss.